2-121530839-T-C

Variant names:

• chr2-121530839-T-C
• rs79645684
• NM_001395891.1:c.196-514A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001395891.1(CLASP1):​c.196-514A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0449 in 666,100 control chromosomes in the GnomAD database, including 899 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.037 (154 hom., cov: 33)
  • Exomes 𝑓: 0.047 (745 hom.)
• Consequence: CLASP1 NM_001395891.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0260
• Publications: 1 publications found

Genes affected

CLASP1 (HGNC:17088): (cytoplasmic linker associated protein 1) CLASPs, such as CLASP1, are nonmotor microtubule-associated proteins that interact with CLIPs (e.g., CLIP170; MIM 179838). CLASP1 is involved in the regulation of microtubule dynamics at the kinetochore and throughout the spindle (Maiato et al., 2003 [PubMed 12837247]).[supplied by OMIM, Mar 2008]

CLASP1-AS1 (HGNC:55328): (CLASP1 antisense RNA 1)

RNU4ATAC (HGNC:34016): (RNA, U4atac small nuclear) The small nuclear RNA (snRNA) encoded by this gene is part of the U12-dependent minor spliceosome complex. In addition to the encoded RNA, this ribonucleoprotein complex consists of U11, U12, U5, and U6atac snRNAs. The U12-dependent spliceosome acts on approximately 700 specific introns in the human genome. Defects in this gene are a cause of microcephalic osteodysplastic primordial dwarfism type 1 (MOPD). [provided by RefSeq, Jul 2011]

RNU4ATAC Gene-Disease associations (from GenCC):

• microcephalic osteodysplastic primordial dwarfism type I

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
• RNU4ATAC spectrum disorder

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Broad Center for Mendelian Genomics, Ambry Genetics, ClinGen
• Roifman syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Illumina
• Lowry-Wood syndrome

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 2-121530839-T-C is Benign according to our data. Variant chr2-121530839-T-C is described in ClinVar as Benign. ClinVar VariationId is 1242503.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.131 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001395891.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLASP1	NM_001395891.1	MANE Select	c.196-514A>G		intron	N/A	NP_001382820.1	A0A8V8TLP7
	CLASP1	NM_015282.3		c.196-514A>G		intron	N/A	NP_056097.1	Q7Z460-1
	CLASP1	NM_001378003.1		c.196-514A>G		intron	N/A	NP_001364932.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLASP1	ENST00000696935.1	MANE Select	c.196-514A>G		intron	N/A	ENSP00000512981.1	A0A8V8TLP7
	CLASP1	ENST00000263710.8	TSL:5	c.196-514A>G		intron	N/A	ENSP00000263710.4	Q7Z460-1
	CLASP1	ENST00000961911.1		c.196-514A>G		intron	N/A	ENSP00000631970.1

Frequencies

GnomAD3 genomes AF: 0.0370 AC: 5635 AN: 152108 Hom.: 153 Cov.: 33

Gnomad AFR AF: 0.0148

Gnomad AMI AF: 0.0526

Gnomad AMR AF: 0.0376

Gnomad ASJ AF: 0.0628

Gnomad EAS AF: 0.139

Gnomad SAS AF: 0.0542

Gnomad FIN AF: 0.0248

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0421

Gnomad OTH AF: 0.0296

GnomAD2 exomes AF: 0.0511 AC: 6238 AN: 121986 AF XY: 0.0504

Gnomad AFR exome AF: 0.0127

Gnomad AMR exome AF: 0.0525

Gnomad ASJ exome AF: 0.0590

Gnomad EAS exome AF: 0.132

Gnomad FIN exome AF: 0.0272

Gnomad NFE exome AF: 0.0423

Gnomad OTH exome AF: 0.0479

GnomAD4 exome AF: 0.0473 AC: 24298 AN: 513874 Hom.: 745 Cov.: 0 AF XY: 0.0472 AC XY: 12962 AN XY: 274568

African (AFR) AF: 0.0154 AC: 225 AN: 14600

American (AMR) AF: 0.0510 AC: 1628 AN: 31894

Ashkenazi Jewish (ASJ) AF: 0.0565 AC: 1078 AN: 19092

East Asian (EAS) AF: 0.115 AC: 3626 AN: 31428

South Asian (SAS) AF: 0.0474 AC: 2851 AN: 60184

European-Finnish (FIN) AF: 0.0287 AC: 935 AN: 32630

Middle Eastern (MID) AF: 0.0253 AC: 58 AN: 2296

European-Non Finnish (NFE) AF: 0.0429 AC: 12579 AN: 293090

Other (OTH) AF: 0.0460 AC: 1318 AN: 28660

GnomAD4 genome AF: 0.0370 AC: 5638 AN: 152226 Hom.: 154 Cov.: 33 AF XY: 0.0362 AC XY: 2695 AN XY: 74422

African (AFR) AF: 0.0149 AC: 619 AN: 41556

American (AMR) AF: 0.0377 AC: 577 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0628 AC: 218 AN: 3470

East Asian (EAS) AF: 0.139 AC: 720 AN: 5164

South Asian (SAS) AF: 0.0539 AC: 260 AN: 4826

European-Finnish (FIN) AF: 0.0248 AC: 263 AN: 10598

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.0421 AC: 2862 AN: 67998

Other (OTH) AF: 0.0293 AC: 62 AN: 2114

Alfa AF: 0.0401 Hom.: 26

Bravo AF: 0.0386

Asia WGS AF: 0.0660 AC: 232 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	6.4
DANN	Benign	0.70
PhyloP100		-0.026
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs79645684; hg19: chr2-122288415;